This is a two center, open label, non-randomized Phase II study of lenvatinib in adult subjects with recurrent or refractory advanced cancers with aberration(s) in FGF/FGFR signaling. Treatment will consist of daily oral administration of Lenvatinib in 28-day cycles.
This exploratory, histology-independent study will enroll up to 39 subjects regardless of FGF/FGFR aberration or cancer type in order to test the hypothesis that subjects with advanced cancers harboring changes in FGF/FGFR-related genes will respond to the multikinase inhibitor lenvatinib at a higher rate than unselected cancer patients, regardless of the tumor histological subtype. Lenvatinib is a multikinase inhibitor that inhibits FGFR1-4 as well as VEGFR1-3, RET, KIT and PDGFR-beta. It inhibits FGFR1 with an IC50 of 46 nmol/L, which is highly potent at a clinically relevant concentration. Fibroblast growth factor (FGF) and FGF receptor (FGFR) pathway aberrations are common in malignancy, making this pathway a potentially appealing target for anti-cancer therapy. Clinical trial data suggest that targeting FGFR is indeed effective in cancer. However, the majority of such data come from trials in patient populations unselected for FGF/FGFR pathway abnormalities. The true response rates or clinical benefits for those whose cancers harbor FGF/FGFR abnormalities may be higher than observed in unselected patient populations.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Lenvatinib is administered orally at a starting dose of 24 mg per day. Lenvatinib is administered in cycles of 28 days.
University of California, San Diego
La Jolla, California, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
Objective Response Rates
Time frame: 2 months
Clinical Benefit Rate (Complete Response, Partial Response, or Stable Disease greater than 6 months)
Time frame: 6 months
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0
Adverse events will be evaluated to determine: * duration (start and end dates) * severity (grade) * seriousness * relationship to study agent * action taken (i.e., none, study agent modification, medical intervention) * outcome (i.e., resolved without sequelae, resolved with sequelae, ongoing)
Time frame: 2 years
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